Influence of terminal functionality on the crystal packing behaviour and cytotoxicity of aromatic oligoamides

Delfosse, Pierre, Seaton, Colin C., Male, Louise, Lord, Rianne M. ORCID: and Pike, Sarah J. (2021) Influence of terminal functionality on the crystal packing behaviour and cytotoxicity of aromatic oligoamides. Frontiers in Chemistry, 9. ISSN 2296-2646

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The synthesis and characterization of three aromatic oligoamides, constructed from the same pyridyl carboxamide core but incorporating distinct end groups of acetyl (Ac) 1, tert-butyloxycarbonyl (Boc) 2 and amine 3 is reported. Single crystal X-ray diffraction analysis of 1–3 and a dimethylsulfoxide (DMSO) solvate of 2 (2-DMSO), has identified the presence of a range of intra- and intermolecular interactions including N-H⋯N, N-H⋯O=C and N-H⋯O=S(CH 3) 2 hydrogen-bonding interactions, C-H⋯π interactions and off-set, face-to-face stacking π-π interactions that support the variety of slipped stack, herringbone and cofacial crystal packing arrangements observed in 1–3. Additionally, the cytotoxicity of this series of aromatic oligoamides was assessed against two human ovarian (A2780 and A2780cisR), two human breast (MCF-7 and MDA-MB-231) cancerous cell lines and one non-malignant human epithelial cell line (PNT-2), to investigate the influence of the terminal functionality of these aromatic oligoamides on their biological activity. The chemosensitivity results highlight that modification of the terminal group from Ac to Boc in 1 and 2 leads to a 3-fold increase in antiproliferative activity against the cisplatin-sensitive ovarian carcinoma cell line, A2780. The presence of the amine termini in 3 gave the only member of the series to display activity against the cisplatin-resistance ovarian carcinoma cell line, A2780cisR. Compound 2 is the lead candidate of this series, displaying high selectivity towards A2780 cancer cells when compared to non-malignant PNT-2 cells, with a selectivity index value >4.2. Importantly, this compound is more selective towards A2780 (cf. PNT-2) than the clinical platinum drugs oxaliplatin by > 2.6-fold and carboplatin by > 1.6-fold.

Item Type: Article
Uncontrolled Keywords: aromatic oligoamides,breast and ovarian cancer,crystallography,cytotoxicity,terminal group,chemistry(all),sdg 3 - good health and well-being ,/dk/atira/pure/subjectarea/asjc/1600
Faculty \ School: Faculty of Science > School of Chemistry
UEA Research Groups: Faculty of Science > Research Centres > Centre for Molecular and Structural Biochemistry
Faculty of Science > Research Groups > Chemistry of Life Processes
Faculty of Science > Research Groups > Chemistry of Materials and Catalysis
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Depositing User: LivePure Connector
Date Deposited: 29 Jul 2021 00:11
Last Modified: 23 Oct 2022 02:50
DOI: 10.3389/fchem.2021.709161


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